Patient-specific neoantigen (TSNA) (TSNA)

Patient-specific neoantigens are unique peptides derived from non-synonymous somatic mutations, such as single nucleotide variants (SNVs) or frameshifts, occurring within a patient's tumor cells (Schumacher & Schreiber, Science 2015). These mutated proteins are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) class I and class II molecules, where they can be recognized by CD8+ and CD4+ T cells, respectively (Blass & Ott, Nature Reviews Clinical Oncology 2021). Because these antigens are absent from the normal genome, they are not subject to central thymic tolerance, making them highly immunogenic and ideal targets for precision immunotherapy (Sahin et al., Nature 2017). Therapeutic approaches include personalized vaccines—utilizing mRNA, DNA, or synthetic peptides—and adoptive cell therapies, such as tumor-infiltrating lymphocytes (TILs) or TCR-engineered T cells (Ott et al., Nature 2017). These strategies aim to stimulate a robust, tumor-specific immune response while minimizing the risk of off-target toxicity to healthy tissues. The identification of these targets typically requires high-throughput sequencing and bioinformatic algorithms to predict which mutations will result in stable peptide-MHC binding (Hu et al., Nature Reviews Genetics 2021).

Other names

Tumor-specific neoantigenNeoepitopeSomatic mutation-derived antigenPersonalized neoantigenTumor-specific antigen (TSA)Neoantigen

Induction of de novo T-cell responses or expansion of existing neoantigen-specific T-cells (CD8+ and CD4+) to recognize and eliminate tumor cells expressing the specific mutated peptide-MHC complex.